BACKGROUND:Our previous study found that Modified Erxian Pill could alleviate inflammation in collagen-induced arthritis rats,but its mechanism needs to be further verified. OBJECTIVE:To analyze the components absorbed in the blood of Modified Erxian Pill,and observe the effect of the drug-containing serum of Modified Erxian Pill on pyroptosis of J774A.1 macrophages. METHODS:(1)Analysis of components absorbed in the blood of Modified Erxian Pill:Ultra-high performance liquid chromatography-high resolution mass spectrometry was used to detect and identify Modified Erxian Pill and its components absorbed in the blood.(2)Effect of the drug-containing serum of Modified Erxian Pill on pyroptosis of J774A.1 macrophages:Molecular docking technology was used to initially verify the sesquiterpenoids and NLRP3 in components absorbed in the blood of Modified Erxian Pill.J774A.1 macrophages were randomly divided into blank control group,lipopolysaccharide+adenosine triphosphate group,and lipopolysaccharide+adenosine triphosphate+Modified Erxian Pill with low(2.5%),medium(5%),and high(10%)dose groups.The release of lactate dehydrogenase in the cell supernatant of each group was detected according to the kit instructions.The levels of interleukin-1β and interleukin-18 in cell supernatant were detected in each group by ELISA.The cell membrane damage was detected by Hoechst/PI staining.The expression levels of NLRP3,Caspase-1,GSDMD,and GSDMD-N protein in the cells of each group were detected by western blot assay. RESULTS AND CONCLUSION:(1)A total of 32 active components of Modified Erxian Pill were identified,and 21 components entered the blood.The main components into blood included a variety of sesquiterpenoids.(2)Molecular docking results showed that 3-O-Acetyl-13-deoxyphomenone,Incensol oxide,Atractylenolide III,Rupestonic acid,and 3,7-Dihydroxy-9,11-eremophiladien-8-one had good binding activity with NLRP3.(3)Compared with the blank control group,lactate dehydrogenase activity and the expression levels of interleukin-1β and interleukin-18 were significantly increased in cell supernatant of lipopolysaccharide+adenosine triphosphate group(P<0.001).Hoechst/PI staining showed that the number of PI-positive cells was significantly increased.After the intervention of lipopolysaccharide+adenosine triphosphate+Modified Erxian Pill group,all of them showed different degrees of reduction.(4)Compared with the blank control group,NLRP3,Caspase-1,GSDMD,and GSDMD-N protein expression levels were significantly increased in the lipopolysaccharide+adenosine triphosphate group(P<0.05).Compared with lipopolysaccharide+adenosine triphosphate group,the protein expressions of NLRP3,Caspase-1,GSDMD,and GSDMD-N were significantly decreased in the lipopolysaccharide+adenosine triphosphate+Modified Erxian Pill group(P<0.05),and had a certain dose dependence.These findings verify that the drug-containing serum of Modified Erxian Pill may inhibit the pyroptosis of J774A.1 macrophages by regulating the NLRP3/Caspase-1/GSDMD pathway.

BACKGROUND:Rheumatoid arthritis is an inflammatory disease.Many studies have shown that wogonin has a good anti-inflammatory effect on rheumatoid arthritis,but its exact efficacy and specific mechanism of action remain to be clarified. OBJECTIVE:To investigate the mechanism of wogonin ameliorating joint inflammation by regulating endoplasmic reticulum stress pathway in rats with collagen-induced arthritis. METHODS:(1)At the animal level:Female Wistar rats were divided into healthy control group,arthritis model group and wogonin treatment group.Rat models of arthritis in the latter two groups were established by subcutaneous injection of bovine type Ⅱ collagen and adjuvant.In the wogonin group,wogonin was given by gavage for 28 consecutive days after modeling.During this period,the rats in each group were weighed,and arthritis score and ankle swelling were measured every 7 days.After the experiment,the pathological changes of the joint were observed,the mRNA and protein levels of endoplasmic reticulum stress pathway GRP78 and CHOP were detected by qRT-PCR,western blot,and immunohistochemistry.(2)At the cellular level,cell counting kit-8 was used to detect the cytotoxic effect of wogonin on fibroblast-like synoviocytes from rats with collagen-induced arthritis.The fibroblast-like synoviocytes induced by thapsigargin were treated with different concentrations of wogonin.The levels of interleukin-1β and tumor necrosis factor-α in the cell supernatant were detected by ELISA,and the intracellular reactive oxygen species in each group were determined by DCFH-DA probe method.The mRNA and protein levels of GRP78,IRE1α,XBP1s and CHOP were detected by qRT-PCR and western blot,respectively. RESULTS AND CONCLUSION:Compared with the healthy control group,arthritis index score and ankle swelling degree in the arthritis model group were increased(P<0.01),synovial hyperplasia,inflammatory cell infiltration,cartilage destruction and bone erosion were observed in pathological sections,and the mRNA and protein expressions of GRP78 and CHOP in the ankle were significantly increased(P<0.01),which were mainly located in synovial tissue and articular surface.Compared with the arthritis model group,the arthritis index score and ankle swelling degree in the wogonin treatment group were decreased(P<0.05),synovial hyperplasia and the number of inflammatory cells were decreased,cartilage destruction and bone erosion were alleviated,the mRNA and protein expression levels of GRP78 and CHOP in the ankle were decreased(P<0.05),particularly in synovial tissue and on the articular surface.There was no significant difference in body mass among the three groups(P>0.05).In the cell experiment,200 μmol/L wogonin significantly reduced the survival rate of fibroblast-like synoviocytes(P<0.01).Compared with the blank control group,the levels of interleukin-1β,tumor necrosis factor-α,content of reactive oxygen species,and mRNA and protein expression of GRP78,IRE1α,XBP1s,and CHOP in the thapsigargin group were significantly increased(P<0.05);compared with the thapsigargin group,50 and 100 μmol/L wogonin significantly reduced the levels of interleukin-1β and tumor necrosis factor-α in the cell supernatant(P<0.05,P<0.01),and 100 μmol/L wogonin significantly reduced the content of reactive oxygen species(P<0.01)and down-regulated the mRNA and protein expression levels of GRP78,IRE1α,XBP1s and CHOP(all P<0.05).These results suggest that wogonin can effectively alleviate joint inflammatory responses in rats with collagen-induced arthritis,and the endoplasmic reticulum stress pathway may be the key target of its intervention.

ObjectiveTo analyze the epidemic characteristics of measles and rubella in Pudong New Area of Shanghai from 2013 to 2022， and to provide data support for the elimination of measles and rubella. MethodsEnzyme linked immunosorbent assay was used to detect IgM antibodies in serum samples. The sequence of 630 nucleotides at the C-terminal of N gene of measles virus was amplified by reverse transcription-polymerase chain reaction and the phylogenic tree was constructed. ResultsA total of 1 529 suspected cases of measles were detected from 2013 to 2022， among which the positive rate of measles IgM antibody was 33.55% （513/1 529）. The highest positive rate （20.73%） was from March to May ， and the positive rate of rubella IgM antibody was 6.80% （104/1 529）. The positive rate of both IgM was higher in males than that in females （P<0.05）. The IgM against measles was mainly detected in 0‒ years old （63.16%， 96/152） and 20‒ years old （45.61%， 161/353）. The IgM against rubella was mainly detected in 10‒20 years old （27.27%， 18/66）. The IgM antibody could be detected more easily from 4 to 28 days after eruption， and the IgM antibody positive rate of measles/rubella from 2020 to 2022 was significantly lower than previous years （2013‒2019）. There were 2 D8 genotype strains， and the rest were H1a gene subtypes. ConclusionThe positive rate of IgM antibodies against measles/rubella in Pudong New Area of Shanghai decreased significantly. People aged 0‒ years and 20‒ years old are more susceptible to measles， and rubella is concentrated in 10‒ years old. It is necessary to strengthen the vaccination of school-age children， in order to achieve the goal of eliminating measles. The age group with high risk of exposure should be checked for vaccination status to ensure the enhanced immunization， and the surveillance of imported measles cases should be strengthened.

Objective:To explore the effect of different concentrations of Chinese herbal formula,Er-miao-san(EMS)immune regulatory gene on Gnαq expression in rats with collagen-induced arthritis(CIA).Methods:In the study,we established a CIA model,and randomly divided into model groups,EMS group with 1.5,3.0 and 4.5 g/kg(L-EMS,M-EMS,H-EMS)were adminis-tered to CIA rats by gavage,methotrexate was used as a positive control group(MTX).The rats in each group were given correspond-ing drugs for treatment,and the normal control group and model group were given the same amount of normal saline gavage.ELISA detects the expression of IL-1β,IL-6 and TNF-α in rats'serum.The mRNA and protein expression of Gnαq were analyzed using qRT-PCR and Western blot.The localization of Gnαq was performed by IHC.Results:The joint of rats in CIA group showed obvious damage,tissue hyperplasia and inflammatory infiltration;the joint tissue destruction and proliferation of MTX and EMS groups were reduced;the expressions of IL-1β,IL-6 and TNF-α in CIA group were extremely increased(P<0.01).The expressions of IL-1β(except H-EMS group),IL-6 and TNF-α in MTX and EMS groups were significantly lower than those in CIA group(P<0.05).The expressions of IL-1β,IL-6 and TNF-α in L-EMS group were lower than those in the M-EMS and H-EMS groups(P<0.05,P<0.01).The expression of Gnαq mRNA and protein in spleen and joints of CIA group were higher than those of Control group(P<0.01).The expression of Gnαq mRNA and protein in spleen and joints of EMS and MTX groups were lower than those of CIA group(P<0.05).The expression of Gnαq mRNA and protein in the dose of 1.5 g/kg of EMS group was lower than those of the other groups(P<0.01,P<0.05).Different degree of posi-tive signal was detected in spleen and joints in different groups.Conclusion:Gnαq is expressed in spleen and joints of CIA rats,may participate in the formation of inflammatory response in CIA rats,and then mediate the formation and development of RA by down-reg-ulating the expression of Gnαq.

The chemical constituents of solid rice culture of the endophytic fungus Aspergillus sp.Dq-25 from barnacle were isolated and purified by silica gel, Sephadex LH-20, C18 reversed silica gel column chromatography and recrystallization.Their structures were identified by the physical and chemical properties, and by various spectroscopic methods.Six compounds were isolated and identified as: demethyldihydropenicillic acid (1), dihydropenicillic acid (2), penicillic acid (3), fortisterol (4), 22E, 24R-3P, 5a-dihydroxyerogosta-7, 22-diene-6-one (5), and (22E, 24R)-ergosterol-7, 22-diene-3β, 5α, 9α-triol-6-one (6).Compound 1 was a new butyrolactone.MTT method was used to analyze cytotoxicity, and the result showed that compound 3 exhibited inhibitory activity on five cell lines, including K562, HeLa, SGC-7901, A542 and BEL-7402, with IC50 values of 38.0 ~ 105.0 μmol/L.

ObjectiveTo investigate the anti-inflammatory effect of the component compatibility of Gentianae Macrophyllae Radix and Clematidis Radix et Rhizoma on the rat model of rheumatoid arthritis （RA） and the mechanism. MethodSeventy-two SPF-grade SD rats （male and female） aged 5 to 6 weeks were selected. Except the blank group， the rat model of collagen-induced arthritis （CIA） was replicated by the type Ⅱ collagen induction method. The 64 rats after successfully modeling were randomly divided into model group， methotrexate group （0.375 mg·kg^-1）， gentianoside with magnoflorine group （150.454 1 mg·kg^-1+5.061 8 mg·kg^-1）， gentianoside with clematichinenoside AR group （150.454 1 mg·kg^-1+16.433 1 mg·kg^-1）， sweroside with magnoflorine group （3.455 8 mg·kg^-1+5.061 8 mg·kg^-1）， sweroside with clematichinenoside AR group （3.455 8 mg·kg^-1+16.433 1 mg·kg^-1）， swertiamarin with magnoflorine group （9.303 2 mg·kg^-1+5.061 8 mg·kg^-1）， and swertiamarin with clematichinenoside AR group （9.303 2 mg·kg^-1+16.433 1 mg·kg^-1）， with 8 rats in each group. Each group was given the corresponding medicinal solution or normal saline by gavage for 15 d. During the experiment， the general status， of rats in each group were observed and recorded. Tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， rheumatoid factor （RF）， C reactive protein （CRP）， prostaglandin E₂ （PGE₂）， and anti-cyclic peptide containing citrulline antibody （anti-CCP Ab） in the serum of rats were measured by enzyme-linked immunosorbent assay （ELISA）. The histopathological changes in rat ankle joints were observed by hematoxylin-eosin （HE） staining. Immunohistochemistry （IHC） and Western blot were used to detect the protein expression of nuclear factor-κB （NF-κB） and vascular endothelial growth factor （VEGF） in rat ankle joints. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of NF-κB and VEGF in rat ankle joints. ResultCompared with those in the blank group， rats in the model group were in poor general conditions with significant foot-plantar swelling， and the content of CRP， anti-CCP Ab， and IL-1β in the rat serum was significantly increased （P<0.01）. In the model group， the tissue structure of the ankle joint was severely damaged， and the protein and mRNA expression of NF-κB and VEGF in the rat ankle joints were significantly up-regulated （P<0.01）. As compared with the model group， the general status of rats in each administration group was significantly improved. The levels of serum TNF-α， IL-1β， RF， CRP， PGE₂， and anti-CCP Ab were reduced to different degrees in these administration groups， among which the effects of the gentianoside with clematichinenoside AR group on down-regulating serum TNF-α and IL-1β， the gentianoside with magnoflorine group on down-regulating serum RF and CRP， the sweroside with magnoflorine group on down-regulating serum PGE₂， and the swertiamarin with clematichinenoside AR group on lowering serum anti-CCP Ab were better than those of administration groups. The histopathological changes in the ankle joint were improved to different degrees. The protein and mRNA expression of NF-κB and VEGF in rat ankle joints in the administration groups was significantly down-regulated （P<0.05， P<0.01）， and the swertiamarin paired with clematichinenoside AR group had the most significant effect. ConclusionThe component compatibility of Gentianae Macrophyllae Radix and Clematidis Radix et Rhizoma exerts a good therapeutic effect on the rat model of RA， and the compatibility of components from the two medicines has a multi-channel， multi-target， and synergistic effect. The five component compatibility patterns， namely gentiobioside with magnoflorine， gentiobioside with clematichinenoside AR， sweroside with clematichinenoside AR， swertiamarin with magnoflorine， and swertiamarin with clematichinenoside AR， all have potential advantages. The mechanism may be related to the reduction of inflammatory factor secretion and the inhibition of abnormal protein and mRNA expression of NF-κB and VEGF.

Objective To explore the effect of topical application of Fushan rheumatism external prescription on inflammatory cytokines and notch2 pathway in rats with collagen-induced arthritis(CIA).Methods 36 female Wistar rats were randomly divided into normal group(n=10)and model group(n=26).CIA model was successfully established in 20 rats,which were randomly divided into model group(n=10)and Fushan rheumatism external prescription group(n= 10).Treatment was initiated on day 14,and 0.4 mL ointment was evenly applied to the ankle joints of rats in Fushan rheumatism external prescription group.Normal group and model group were topical smeared with the same volume of normal saline.Activity was taken twice a day for 42 days.The joint swelling of rats was observed every week and the arthritis index was scored.Thereafter blood was collected from abdominal aorta,and then ankle joint,spleen,liver,and kidney of rats were taken out after the end of the interventions.The severity of arthritis and the pathological changes of ankle joint,liver and kidney were evaluated by HE staining;Inflammatory cytokines expression in serum were detected by ELISA;The expression of Notch2,Delta-like ligand protein 1(delta-like ligand protein-1,DLL1)and nuclear factor-κ Bp65(nuclear factor-κ Bp65,NF-κ Bp65)mRNA and protein in synovium of ankle joints and spleen were detected by qRT-PCR and Western blot,and its positive expression in ankle joints were detected by immunohistochemical method;The changes of liver and kidney function of rats in each group were detected in serum.Results Compared with normal group,the arthritis index score in model group were increased(P<0.01),joint injury and pathological score were increased(P<0.01),the levels of inflammatory cytokines TNF-α,IL-6,IL-17 and IFN-γ in serum were increased(P<0.01),the expression of Notch2,DLL1 and NF-κBp65 mRNA and protein in joints and spleen were increased(P<0.01),and the positive expression in joints were also increased(P<0.01);Compared with model group,the arthritis index score in Fushan rheumatism external prescription group were decreased(P<0.05,P<0.01),joint injury and pathological score were decreased(P<0.01),the levels of inflammatory cytokines TNF-α,IL-6,IL-17 and IFN-γ in serum were decreased(P<0.01),the expression of Notch2,DLL1 and NF-κBp65 mRNA and protein in joints and spleen were decreased(P<0.01),and the positive expression in joints were also decreased(P<0.01).In addition,no noticeable tissue damages were observed in liver and kidney in Fushan rheumatism external prescription group,and the levels of aspartate aminotransferase(AST),alanine aminotransferase(ALT),blood urea nitrogen(BUN)and creatinine(Cr)in serum were no changes(P>0.05).Conclusion Fushan rheumatism external prescription relieves arthritis symptoms and joint injury in CIA rats,and has no toxic and side effects on liver and kidney.Its mechanism may be related to the reduction of inflammatory cytokines and down-regulation of Nocth2 pathway.

Objective:To investigate the mechanism of methotrexate in the treatment of rheumatoid arthritis (RA) by constructing a rat model of collagen-induced arthritis (CIA) and using non-targeted metabolomics.Methods:Enzyme-linked immunosorbent assay (ELISA) was used to determine the contents of TNF-α, IL-1β, IL-6, IL-4 and IL-10 in serum. HE staining and Masson staining were used to observe the histological changes of joints in each group. Non-targeted gas chromatography-mass spectrometry metabolomics technique was used to screen the expression profiles of differential metabolites in serum and cluster analysis and KEGG enrichment analysis were performed to screen the differential metabolic pathways, and real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the key enzymes in the differential metabolic pathways. All experimental data conforming to the normal distribution were compared between groups using one-way ANOVA, and P<0.05 was considered statistically significant. Results:MTX significantly improved the joint inflammatory response and arthritis score and increased the body weight of CIA rats. The results of HE and Masson staining showed that MTX could ameliorate the erosion of articular cartilage by synovial tissue in CIA rats. ELISA results showed that MTX significantly decreased the contents of TNF-α [(191.2±17.4)pg/ml, F=40.31, P<0.001], IL-1β[(28.4±1.2)pg/ml, F=10.11, P=0.012] and IL-6[(118.7±1.4)pg/ml, F=829.40, P<0.001] in the serum and increased the contents of IL-4 [(49.3±3.3)pg/ml, F=33.44, P<0.001] and IL-10 [(30.2±0.7)pg/ml, F=33.44, P<0.001] in the serum of CIA rats. Non-targeted metabolomics technique showed MTX had an effect on metabolites such as phosphocholine, palmitic acid, oleic acid, and choline in the serum of CIA rats. KEGG pathway enrichment analysis showed that MTX had an effect on glycerophospholipid metabolism( P<0.01)and sphingolipid metabolism( P<0.05)in CIA rats. qRT-PCR results showed that MTX could down-regulate the expression of the key enzymes such as Plb1 [(1.00±0.49), F=8.23, P=0.019], Gpcpd1[(1.10±0.09), F=8.19, P=0.019], Chka [(1.33±0.19), F=33.00, P<0.001], Chkb [(2.07±1.21), F=8.20, P=0.019]and Phospho1 [(1.07±0.14), F=13.58, P=0.006]in the glycerophospholipid metabolic pathway in the synovial membrane of CIA rats, and can also down-regulate the expression of the key enzymes Kdsr [(1.24±0.32), F=13.85, P=0.006], Plpp1 [(1.61±0.32), F=11.95, P=0.003) and Degs1 [(1.21±0.15, F=46.55, P<0.001]in the sphingolipid metabolic pathway. Conclusion:The biological mechanism of MTX in the treatment of rheumatoid arthritis may be related to the down-regulation of glycerophospholipid metabolism and sphingolipid metabolism pathway metabolic levels in the body.

ObjectiveTo observe the clinical effect of Xijiao Dihuangtang combined with acupuncture on the treatment of systemic lupus erythematosus （SLE） with syndrome of intense heat toxin. MethodA total of 102 cases of SLE with syndrome of intense heat toxin （admitted from January 2020 to December 2021） were divided into a control group and an observation group by random number table method， with 51 cases in each group. Patients in the control group received conventional western medicine treatment （hydroxychloroquine sulfate + poonisone acetate tablets）. Patients in the observation group were given Xijiao Dihuangtang combined with acupuncture based on the treatment of the control group. Clinical efficacy， onset time， symptom improvement time， skin lesion regression time， and hospital stays were recorded. Blood routine index change， 24 h urine protein levels， double-stranded DNA （ds-DNA） antibodies resistance index changes， traditional Chinese medicine （TCM） syndrome integral changes， and changes in serum cytokine indexes， blood rheology indexes， and T lymphocyte subsets indexes were observed. SLE changes in disease activity index （SLEDAI-2000）， quality of life （SF-36） scores， and adverse reactions were explored. ResultThe total effective rate was 96.08% （49/51） in the observation group， higher than 84.31% （43/51） in the control group （χ²=3.991， P<0.05）. The onset time， symptom improvement time， skin lesion regression time， and hospital stays in the observation group were shorter than those in the control group （P<0.05，P<0.01）. Before treatment， erythrocyte sedimentation rate （ESR）， platelet count （PLT）， hemoglobin （HGB）， white blood cell count （WBC）， and other blood routine indexes， 24h urinary protein levels， anti-ds-DNA， TCM syndrome integral core， serum cytokine indexes including interleukin-4 （IL-4）， IL-6， soluble interleukin-2 receptor （sIL-2R）， blood rheology indexes （fibrinogen， plasma viscosity， and whole blood viscosity），T lymphocyte subsets indexes （CD4⁺， CD8⁺， and CD4⁺/CD8⁺）， SLEDAI-2000， and SF-36 score comparison in both groups had no statistical significance. After treatment， the above indicators were improved in each group （P<0.05）， and the indicators in the observation group was better than that in the control group （P<0.05）. In terms of the adverse reactions， there was 1 case of digestive tract reaction， 1 case of elevated aminotransferase， and 1 case of insomnia in the observation group. There were 2 cases of digestive tract reaction，1 case of infection， and 1 case of elevated transaminase in the control group. The difference of the adverse reactions between the two groups had no statistical significance. ConclusionXijiao Dihuangtang combined with acupuncture has good clinical effect on the treatment of SLE with syndrome of intense heat toxin， and the method is safe， reliable， and worthy of application.

Objective:To analyze the efficacy and safety of curcumin in the treatment of knee osteoarthritis.Methods:The randomized controlled trials of curcumin in the treatment of knee osteoarthritis published from January 2011 to August 2021 were retrieved. The bias risk of the included literatures was evaluated by Revman 5.3 software, and the efficacy related indexes and the incidence of adverse events were analyzed by Stata 16.0 software. The weighted mean difference ( WMD) was calculated for the difference of efficacy indexes, the odds ratio ( OR) was calculated for the difference of safety indexes, the difference was compared by t test. Results:① A total of 9 relevant literatures were included, all of which were in English. ② A total of 724 patients were included in the study, of which 383 were treated with curcumin capsules and 341 were treated with placebo. ③ The visual analogue scale/score (VAS) of patients treated with oral curcumin at 3-4, 6 and 8 weeks were significantly lower than those of patients treated with oral placebo, the differences were statistically significant [weighted mean difference ( WMD)=-1.09, 95% CI (-1.44, -0.73), P<0.001; WMD=-1.52, 95% CI (-2.35, -0.69), P<0.001; WMD=-1.20, 95% CI(-1.71, -0.69), P<0.001]. ④ The western Ontario and McMaster universities osteoarthritis index (WOMAC) scores of patients treated with oral curcumin for 3-4 and 6-8 weeks were significantly lower than those of patients treated with oral placebo, and the differences were statistically significant [ WMD=-7.96, 95% CI(-14.89, -1.04), P=0.020; WMD=-15.34, 95% CI(-20.51, -10.18), P<0.001]. Specifically, the WOMAC pain and stiffness scores of patients treated with oral curcumin for 6-8 weeks were significantly lower than those of patients treated with oral placebo, and the differences were statistically significant [ WMD=-2.16, 95% CI(-3.69, -0.63), P=0.010; WMD=-1.00, 95% CI (-1.54, -0.46), P<0.001]. The WOMAC joint function scores of patients treated with oral curcumin for 3-4 and 6-8 weeks were significantly lower than those of patients treated with oral placebo, the difference was statistically significant [ WMD=-3.21, 95% CI(-4.51, -1.92), P<0.001; WMD=-7.07, 95% CI(-11.19, -2.94), P<0.001]. ⑤ There was no significant difference in the incidence of adverse events between oral curcumin and placebo [ OR=1.19, 95% P(0.74, 1.90), P=0.478]. Conclusion:Compared with placebo, oral curcumin can significantly alleviate the pain, stiffness and joint function of patients with knee osteoarthritis, and its safety is similar to placebo.